Single-molecule electrical sequencing of DNA

Two paradigm shifts in DNA sequencing technologies—from bulk to single molecules and from optical to electrical detection—are expected to realize label-free, low-cost DNA sequencing that does not require PCR amplification, leading to high-throughput third-generation sequencing technologies for personalized medicine. Although bio-nanopores, solid-state nanopores and gating nanopores have been proposed as third-generation DNA sequencing devices, a critical breakthrough has been made by demonstrating a novel technique for determining sequences of long, single-stranded DNA molecules using electrical signals. Here we report on single-molecule electrical sequencing of DNA and RNA by a hybrid method of identifying single base molecules via a tunnelling current and random sequencing. Our method reads sequences of 6 types of DNA oligomers composed of 3 base molecules. The complete sequence of a microRNA composed of 7 base molecules was also identified by creating a composite of overlapping fragment sequences randomly determined using a tunnelling current conducted by single base molecules as they passed between a pair of nanoelectrodes.

Scientific Reports 2, doi: 10.1038/srep00501 (2012).